Cancer Research Audrey Hepburn EMT and Cancer Progression and Treatment
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pihan, G. A.
Right arrow Articles by Doxsey, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pihan, G. A.
Right arrow Articles by Doxsey, S. J.
[Cancer Research 61, 2212-2219, March 1, 2001]
© 2001 American Association for Cancer Research

Tumor Biology

Centrosome Defects Can Account for Cellular and Genetic Changes That Characterize Prostate Cancer Progression1

German A. Pihan2, Aruna Purohit, Janice Wallace, Raji Malhotra, Lance Liotta and Stephen J. Doxsey2

Department of Pathology [G. A. P., J. W., R. M.] and Program in Molecular Medicine [A. P., S. J. D.], University of Massachusetts Medical School, Worcester, Massachusetts 01655, and Department of Pathology, National Cancer Institute, Bethesda, Maryland 20892 [L. L.]

Factors that determine the biological and clinical behavior of prostate cancer are largely unknown. Prostate tumor progression is characterized by changes in cellular architecture, glandular organization, and genomic composition. These features are reflected in the Gleason grade of the tumor and in the development of aneuploidy. Cellular architecture and genomic stability are controlled in part by centrosomes, organelles that organize microtubule arrays including mitotic spindles. Here we demonstrate that centrosomes are structurally and numerically abnormal in the majority of prostate carcinomas. Centrosome abnormalities increase with increasing Gleason grade and with increasing levels of genomic instability. Selective induction of centrosome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic characteristics of high-grade prostate carcinoma. Cells that transiently or permanently express pericentrin exhibit severe centrosome and spindle defects, cellular disorganization, genomic instability, and enhanced growth in soft agar. On the basis of these observations, we propose a model in which centrosome dysfunction contributes to the progressive loss of cellular and glandular architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.




This article has been cited by other articles:


Home page
 FASEB J.Home page
S. Yang, X. Liu, Y. Yin, M. N. Fukuda, and J. Zhou
Tastin is required for bipolar spindle assembly and centrosome integrity during mitosis
FASEB J, June 1, 2008; 22(6): 1960 - 1972.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
M C. Miller, G. V Doyle, and L. W M M Terstappen
Monitoring and Characterization of CTC in Cancer Patients
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 617 - 624.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Z. Matijasevic, H. A. Steinman, K. Hoover, and S. N. Jones
MdmX Promotes Bipolar Mitosis To Suppress Transformation and Tumorigenesis in p53-Deficient Cells and Mice
Mol. Cell. Biol., February 15, 2008; 28(4): 1265 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
W. J. Chng, E. Braggio, G. Mulligan, B. Bryant, E. Remstein, R. Valdez, A. Dogan, and R. Fonseca
The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition
Blood, February 1, 2008; 111(3): 1603 - 1609.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
C. Kasbek, C.-H. Yang, A. M. Yusof, H. M. Chapman, M. Winey, and H. A. Fisk
Preventing the Degradation of Mps1 at Centrosomes Is Sufficient to Cause Centrosome Reduplication in Human Cells
Mol. Biol. Cell, November 1, 2007; 18(11): 4457 - 4469.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. I. van de Wetering and C. M. Knudson
Chromosomal Instability and Supernumerary Centrosomes Represent Precursor Defects in a Mouse Model of T-Cell Lymphoma
Cancer Res., September 1, 2007; 67(17): 8081 - 8088.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Rebacz, T. O. Larsen, M. H. Clausen, M. H. Ronnest, H. Loffler, A. D. Ho, and A. Kramer
Identification of Griseofulvin as an Inhibitor of Centrosomal Clustering in a Phenotype-Based Screen
Cancer Res., July 1, 2007; 67(13): 6342 - 6350.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. Tanaka, Y. Hashimoto, T. Ito, K. Kondo, M. Higashiyama, S. Tsunoda, C. Ortiz, Y. Sakai, J. Inazawa, and Y. Shimada
The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma
Clin. Cancer Res., February 15, 2007; 13(4): 1331 - 1340.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Shao, Y. Wang, S. Jin, Y. Song, X. Wang, W. Fan, Z. Zhao, M. Fu, T. Tong, L. Dong, et al.
Gadd45a Interacts with Aurora-A and Inhibits Its Kinase Activity
J. Biol. Chem., September 29, 2006; 281(39): 28943 - 28950.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
O. Date, M. Katsura, M. Ishida, T. Yoshihara, A. Kinomura, T. Sueda, and K. Miyagawa
Haploinsufficiency of RAD51B Causes Centrosome Fragmentation and Aneuploidy in Human Cells.
Cancer Res., June 15, 2006; 66(12): 6018 - 6024.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
M. C Fleisch, C. A Maxwell, and M.-H. Barcellos-Hoff
The pleiotropic roles of transforming growth factor beta in homeostasis and carcinogenesis of endocrine organs.
Endocr. Relat. Cancer, June 1, 2006; 13(2): 379 - 400.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
W. J. Chng, G. J. Ahmann, K. Henderson, R. Santana-Davila, P. R. Greipp, M. A. Gertz, M. Q. Lacy, A. Dispenzieri, S. Kumar, S. V. Rajkumar, et al.
Clinical implication of centrosome amplification in plasma cell neoplasm
Blood, May 1, 2006; 107(9): 3669 - 3675.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
F. Suizu, A. Ryo, G. Wulf, J. Lim, and K. P. Lu
Pin1 Regulates Centrosome Duplication, and Its Overexpression Induces Centrosome Amplification, Chromosome Instability, and Oncogenesis
Mol. Cell. Biol., February 15, 2006; 26(4): 1463 - 1479.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J.-M. Peloponese Jr., K. Haller, A. Miyazato, and K.-T. Jeang
Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein
PNAS, December 27, 2005; 102(52): 18974 - 18979.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. S. Golubkov, A. V. Chekanov, S. J. Doxsey, and A. Y. Strongin
Centrosomal Pericentrin Is a Direct Cleavage Target of Membrane Type-1 Matrix Metalloproteinase in Humans but Not in Mice: POTENTIAL IMPLICATIONS FOR TUMORIGENESIS
J. Biol. Chem., December 23, 2005; 280(51): 42237 - 42241.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
M. Fenech
The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis
Mutagenesis, July 1, 2005; 20(4): 255 - 269.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. S. Golubkov, S. Boyd, A. Y. Savinov, A. V. Chekanov, A. L. Osterman, A. Remacle, D. V. Rozanov, S. J. Doxsey, and A. Y. Strongin
Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Exhibits an Important Intracellular Cleavage Function and Causes Chromosome Instability
J. Biol. Chem., July 1, 2005; 280(26): 25079 - 25086.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
A. Can, O. Semiz, and O. Cinar
Bisphenol-A induces cell cycle delay and alters centrosome and spindle microtubular organization in oocytes during meiosis
Mol. Hum. Reprod., June 1, 2005; 11(6): 389 - 396.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. Tanaka, Y. Hashimoto, T. Ito, T. Okumura, T. Kan, G. Watanabe, M. Imamura, J. Inazawa, and Y. Shimada
The Clinical Significance of Aurora-A/STK15/BTAK Expression in Human Esophageal Squamous Cell Carcinoma
Clin. Cancer Res., March 1, 2005; 11(5): 1827 - 1834.
[Abstract] [Full Text] [PDF]

Home page
 JDRHome page
S.C. Reshmi and S.M. Gollin
Chromosomal Instability in Oral Cancer Cells
Journal of Dental Research, February 1, 2005; 84(2): 107 - 117.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
N. J. Quintyne, J. E. Reing, D. R. Hoffelder, S. M. Gollin, and W. S. Saunders
Spindle Multipolarity Is Prevented by Centrosomal Clustering
Science, January 7, 2005; 307(5706): 127 - 129.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Fan, T. S. Kumaravel, F. Jalali, P. Marrano, J. A. Squire, and R. G. Bristow
Defective DNA Strand Break Repair after DNA Damage in Prostate Cancer Cells: Implications for Genetic Instability and Prostate Cancer Progression
Cancer Res., December 1, 2004; 64(23): 8526 - 8533.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
P Dey
Aneuploidy and malignancy: an unsolved equation
J. Clin. Pathol., December 1, 2004; 57(12): 1245 - 1249.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Hida, Y. Hida, D. N. Amin, A. F. Flint, D. Panigrahy, C. C. Morton, and M. Klagsbrun
Tumor-Associated Endothelial Cells with Cytogenetic Abnormalities
Cancer Res., November 15, 2004; 64(22): 8249 - 8255.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. G. Hayward, R. B. Clarke, A. J. Faragher, M. R. Pillai, I. M. Hagan, and A. M. Fry
The Centrosomal Kinase Nek2 Displays Elevated Levels of Protein Expression in Human Breast Cancer
Cancer Res., October 15, 2004; 64(20): 7370 - 7376.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
M. Martinez-Campos, R. Basto, J. Baker, M. Kernan, and J. W. Raff
The Drosophila pericentrin-like protein is essential for cilia/flagella function, but appears to be dispensable for mitosis
J. Cell Biol., June 7, 2004; 165(5): 673 - 683.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Delattre and P. Gonczy
The arithmetic of centrosome biogenesis
J. Cell Sci., May 1, 2004; 117(9): 1619 - 1630.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Chen, A. Purohit, E. Halilovic, S. J. Doxsey, and A. C. Newton
Centrosomal Anchoring of Protein Kinase C {beta}II by Pericentrin Controls Microtubule Organization, Spindle Function, and Cytokinesis
J. Biol. Chem., February 6, 2004; 279(6): 4829 - 4839.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
N. AHMAD
Polo-like kinase (Plk) 1: a novel target for the treatment of prostate cancer
FASEB J, January 1, 2004; 18(1): 5 - 7.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. H. Yang, D. Kaushal, S. K. Rehen, K. Kriedt, M. A. Kingsbury, M. J. McConnell, and J. Chun
Chromosome Segregation Defects Contribute to Aneuploidy in Normal Neural Progenitor Cells
J. Neurosci., November 12, 2003; 23(32): 10454 - 10462.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. Gromley, A. Jurczyk, J. Sillibourne, E. Halilovic, M. Mogensen, I. Groisman, M. Blomberg, and S. Doxsey
A novel human protein of the maternal centriole is required for the final stages of cytokinesis and entry into S phase
J. Cell Biol., May 12, 2003; 161(3): 535 - 545.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. A. Pihan, J. Wallace, Y. Zhou, and S. J. Doxsey
Centrosome Abnormalities and Chromosome Instability Occur Together in Pre-invasive Carcinomas
Cancer Res., March 15, 2003; 63(6): 1398 - 1404.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Li, J. Zhu, P. F. Firozi, J. L. Abbruzzese, D. B. Evans, K. Cleary, H. Friess, and S. Sen
Overexpression of Oncogenic STK15/BTAK/Aurora A Kinase in Human Pancreatic Cancer
Clin. Cancer Res., March 1, 2003; 9(3): 991 - 997.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. J. Keats, T. Reiman, C. A. Maxwell, B. J. Taylor, L. M. Larratt, M. J. Mant, A. R. Belch, and L. M. Pilarski
In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression
Blood, February 15, 2003; 101(4): 1520 - 1529.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
K. Neben, C. Giesecke, S. Schweizer, A. D. Ho, and A. Kramer
Centrosome aberrations in acute myeloid leukemia are correlated with cytogenetic risk profile
Blood, January 1, 2003; 101(1): 289 - 291.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
B. Spankuch-Schmitt, J. Bereiter-Hahn, M. Kaufmann, and K. Strebhardt
Effect of RNA Silencing of Polo-Like Kinase-1 (PLK1) on Apoptosis and Spindle Formation in Human Cancer Cells
J Natl Cancer Inst, December 18, 2002; 94(24): 1863 - 1877.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
S. Sen, H. Zhou, R.-D. Zhang, D. S. Yoon, F. Vakar-Lopez, S. Ito, F. Jiang, D. Johnston, H. B. Grossman, A. C. Ruifrok, et al.
Amplification/Overexpression of a Mitotic Kinase Gene in Human Bladder Cancer
J Natl Cancer Inst, September 4, 2002; 94(17): 1320 - 1329.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Bergoglio, M.-J. Pillaire, M. Lacroix-Triki, B. Raynaud-Messina, Y. Canitrot, A. Bieth, M. Gares, M. Wright, G. Delsol, L. A. Loeb, et al.
Deregulated DNA Polymerase {beta} Induces Chromosome Instability and Tumorigenesis
Cancer Res., June 1, 2002; 62(12): 3511 - 3514.
[Abstract] [Full Text] [PDF]

Home page
 Cell Growth Differ.Home page
M. R. Flory, M. Morphew, J. D. Joseph, A. R. Means, and T. N. Davis
Pcp1p, an Spc110p-related Calmodulin Target at the Centrosome of the Fission Yeast Schizosaccharomyces pombe
Cell Growth Differ., February 1, 2002; 13(2): 47 - 58.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
W. L. Lingle, S. L. Barrett, V. C. Negron, A. B. D'Assoro, K. Boeneman, W. Liu, C. M. Whitehead, C. Reynolds, and J. L. Salisbury
Centrosome amplification drives chromosomal instability in breast tumor development
PNAS, February 19, 2002; 99(4): 1978 - 1983.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.